Orphan receptor GPR158 controls stress-induced depression

Laurie P Sutton; Cesare Orlandi; Chenghui Song; Won Chan Oh; Brian S Muntean; Keqiang Xie; Alice Filippini; Xiangyang Xie; Rachel Satterfield; Jazmine D W Yaeger; Kenneth J Renner; Samuel M Young; Baoji Xu; Hyungbae Kwon; Kirill A Martemyanov

doi:10.7554/eLife.33273

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Orphan receptor GPR158 controls stress-induced depression

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Orphan receptor GPR158 controls stress-induced depression

Laurie P Sutton, Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, …

eLife, Vol.7, e33273

02/08/2018

DOI: 10.7554/eLife.33273

PMCID: PMC5823542

PMID: 29419376

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Abstract

Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the PFC in a glucocorticoid-dependent manner. Viral overexpression of GPR158 in the PFC induced depressive-like behaviors. In contrast GPR158 ablation, led to a prominent antidepressant-like phenotype and stress resiliency. We found that GPR158 exerts its effects via modulating synaptic strength altering AMPA receptor activity. Taken together, our findings identify a new player in mood regulation and introduce a pharmacological target for managing depression.

Details

Title: Subtitle: Orphan receptor GPR158 controls stress-induced depression
Creators: Laurie P Sutton - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Cesare Orlandi - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Chenghui Song - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Won Chan Oh - Max Planck Florida Institute for Neuroscience, Jupiter, United States
Brian S Muntean - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Keqiang Xie - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Alice Filippini - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
Xiangyang Xie - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Rachel Satterfield - Max Planck Florida Institute for Neuroscience, Jupiter, United States
Jazmine D W Yaeger - Center for Brain and Behavior Research, University of South Dakota, Vermillion, United States, Department of Biology, University of South Dakota, Vermillion, United States
Kenneth J Renner - Center for Brain and Behavior Research, University of South Dakota, Vermillion, United States, Department of Biology, University of South Dakota, Vermillion, United States
Samuel M Young - Max Planck Florida Institute for Neuroscience, Jupiter, United States, Department of Anatomy and Cell Biology, University of Iowa, Iowa, United States, Aging Mind and Brain Initiative, University of Iowa, Iowa, United States, Department of Otolaryngology, Carver College of Medicine, University of Iowa, Iowa, United States
Baoji Xu - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Hyungbae Kwon - Max Planck Florida Institute for Neuroscience, Jupiter, United States, Max Planck Institute of Neurobiology, Martinsried, Germany
Kirill A Martemyanov - Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
Resource Type: Journal article
Publication Details: eLife, Vol.7, e33273
DOI: 10.7554/eLife.33273
PMID: 29419376
PMCID: PMC5823542
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Grant note: DOI: 10.13039/100000025, name: National Institute of Mental Health, award: MH105482; DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute, award: HL105550; DOI: 10.13039/100000025, name: National Institute of Mental Health, award: MH107460; DOI: 10.13039/100000026, name: National Institute on Drug Abuse, award: DA019921; DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: DC014093; DOI: 10.13039/100008893, name: University of Iowa; DOI: 10.13039/501100004189, name: Max-Planck-Gesellschaft; DOI: 10.13039/501100000024, name: Canadian Institutes of Health Research
Language: English
Date published: 02/08/2018
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984025369102771

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